Short-term fasting and lipolytic activity in rat adipocytes.

The aim of this experiment was to study the influence of 18-hour food deprivation on basal and stimulated lipolysis in adipocytes obtained from young male Wistar rats. Fat cells from fed and fasted rats were isolated from the epididymal adipose tissue by collagenase digestion. Adipocytes were incubated in Krebs-Ringer buffer (pH 7.4, 37 degrees C) without agents affecting lipolysis and with different lipolytic stimulators (epinephrine, forskolin, dibutyryl-cAMP, theophylline, DPCPX, amrinone) or inhibitors (PIA, H-89, insulin). After 60 min of incubation, glycerol and, in some cases, also fatty acids released from adipocytes to the incubation medium were determined. Basal lipolysis was substantially potentiated in cells of fasted rats in comparison to adipocytes isolated from fed animals. The inhibition of protein kinase A activity by H-89 partially suppressed lipolysis in both groups of adipocytes, but did not eliminate this difference. The agonist of adenosine A (1) receptor also did not suppress fasting-enhanced basal lipolysis. The epinephrine-induced triglyceride breakdown was also enhanced by fasting. Similarly, the direct activation of adenylyl cyclase by forskolin or protein kinase A by dibutyryl-cAMP resulted in a higher lipolytic response in cells derived from fasted animals. These results indicate that the fasting-induced rise in lipolysis results predominantly from changes in the lipolytic cascade downstream from protein kinase A. The antagonism of the adenosine A (1) receptor and the inhibition of cAMP phosphodiesterase also induced lipolysis, which was potentiated by food deprivation. Moreover, the rise in basal and epinephrine-stimulated lipolysis in adipocytes of fasted rats was shown to be associated with a diminished non-esterified fatty acids/glycerol molar ratio. This effect was presumably due to increased re-esterification of triglyceride-derived fatty acids in cells of fasted rats. Comparing fed and fasted rats for the antilipolytic effect of insulin in adipocytes revealed that short-term food deprivation resulted in a substantial deterioration of the ability of insulin to suppress epinephrine-induced lipolysis.     

Lipoprotein lipase in rat lung. The effect of fasting.

We measured lipoprotein lipase activity in dried defatted preparations of rat lung using doubly labeled chylomicron triglyceride as substrate. The enzyme activity was linear for the first hour of incubation at 37 degrees C, had a pH optimum of 8.1 and was completely inhibited by 0.5 M NaC1. Lungs from fed rats hydrolyzed chylomicron triglyceride at a rate of 13.00 mumoles/g per h; the activity rate was unchanged by fasting 8-72 h. Heparin infusion into isolated lungs caused immediate release of lipoprotein lipase to the venous effluent. The activity released was equivalent to about 10% of total lung lipoprotein lipase activity in both fed and fasted rats. Since the ability to remove blood triglyceride is directly related to the level of lipoprotein lipase activity, these findings indicate that the lung is one of the few tissues able to remove efficiently blood triglyceride during fasting.     

Sodium sparing effect of alanine in fasting obese females.

In obese females, 50 g of alanine given orally on the fifth day of fasting, produced a decrease in urinary sodium that persisted the following day. Plasma renin did not increase the day following alanine intake.     

Hyperlipoproteinemia in fasting ponies

Ponies fasted for up to 8 days showed, both by agarose electrophoresis and preparative ultracentrifugation, the appearance of a pre-beta-migrating, very low density lipoprotein fraction in plasma. This lipoprotein differs from the very low density lipoprotein found in humans and rats in that it contains a relatively smaller amount of total cholesterol, 85% of which is present in the unesterified form. By the 8th day of fasting, plasma triglyceride concentrations had increased from a prefasting level of 20 mg/dl to as high as 1000 mg/dl. The increase in plasma lipid concentrations as a result of fasting was highly variable. Accumulation of plasma cholesterol and triglyceride after injection of Triton WR 1339 was not related to the degree of fasting hyperlipidemia. This suggests that the hyperlipoproteinemia of fasting may result from an impaired utilization of very low density lipoproteins.     

Insulin-stimulated glucose uptake and fasting blood glucose.

Changes in insulin-stimulated glucose metabolism were studied in young and aged subjects, subjects with impaired glucose tolerance, and patients with NIDDM by means of the glucose clamp technique. The diabetic group includes obese and non-obese patients treated without insulin and non-obese patients treated with insulin. The glucose disposal rate (GDR) was decreased in aged subjects (5.8 +/- 0.4 mg/kg/min) compared with young controls (7.4 +/- 0.3 mg/kg/min). In patients with IGT, it was further decreased to 3.6 +/- 0.5 mg/kg/min, which was comparable to the rate in NIDDM without insulin treatment (3.3 +/- 0.4 mg/kg/min). There were no differences in the GDR between obese (3.0 +/- 0.3 mg/kg/min) and non-obese (3.4 +/- 0.6 mg/kg/min) diabetic patients. In insulin-treated diabetic patients, GDR ranged widely, but the mean value was partially normalized (5.2 +/- 0.9 mg/kg/min). In the diabetic group, no correlation was observed between fasting blood glucose and GDR. These results suggest that in the course of developing NIDDM, a decrease in insulin-stimulated glucose uptake precedes a rise in fasting blood glucose. Thus, as previously reported for Caucasian NIDDM patients, resistance to insulin-stimulated glucose uptake may be one of the basic defects in Japanese patients with NIDDM. The degree of glycemia, however, is not directly related to the magnitude of the defect in insulin action.     

Impaired regulation of corticosterone levels during fasting in aging rats.

The concentration of corticosterone in aortal blood of 3-day fasted rats decreases approximately 75% between 2- and 24-months of age. The reduced level of hormone in aging rats is not attributable to an enhanced rate of corticosterone utilization from the blood or to a diminished steroidogenic capacity of the adrenal cortex, but apparently reflects a deficiency in extraadrenal regulatory mechanisms.     

Effects of total fasting in obese women. I. Response of the thyroid.

The values of serum T4, T3, T4/T3, RT3U, FT4I, PBI, ATR, TSH, 132I uptake and antibodies against thyreoglobulin were estimated in non-obese, healthy women and in obese women with a stabile body weight on total fasting of 14 days. Obesity with no dietary restriction compared with normal controls was accompanied by a tendency to higher serum levels of T4 and T3 and prolonged ATR. Other indicators of thyroid function remained unchanged. Total fasting led to a decrease of serum T3 and to an increase of FT4I and RT3U. The remaining tests were unchanged. These results are conform with a decreased transformation of T4 into T3 in the periphery. The participation of the hypothalamus and hypophysis to adaptation of the thyroid to fasting was discussed.     

Diurnal variations and effects of fasting on blood constituents in minipigs.

We examined the diurnal variations and the effects of 48-hour fasting on hematological and serum biochemical values to obtain basic physiological data on ten male and seven female G?ttingen minipigs 6 to 16 months of age. For all hematological parameters examined (RBC, HCT, HGB, WBC and PLT), there was no diurnal variation in either sex, but red blood cell parameters were affected by fasting, with an increase in males and a decrease in females. Three serum biochemical parameters (GOT, UN and i.p.) for males and four (GOT, UN, Ca and i.p.) for females exhibited diurnal variation. These variations were eliminated by fasting. The BIL level in males was increased by fasting, and the color of serum was yellowish. Fe concentration in both sexes and CRE and Mg levels in males were decreased by fasting. These findings are basic data for various experiments on minipigs, and indicate that great care is required in establishing feeding times and fasting intervals and in the analysis of results of experiments on minipigs.     

Kinetic properties of bilirubin UDP-glucuronyltransferase in squirrel monkeys exhibiting fasting hyperbilirubinemia.

1. Bolivian squirrel monkeys (BoSM), unlike Brazilian squirrel monkeys (BrSM), exhibit a marked fasting hyperbilirubinemia (FH) and serve as animal models for Gilbert's syndrome type I. 2. Compared to BrSM, BoSM possess a higher apparent UDPGAKm (0.51 vs 0.29 mM) and lower Vm (0.36 vs 0.48 nmol BR conjugated/min per mg microsomal protein) for hepatic bilirubin (BR) UDP-glucuronyl-transferase (BR UDPG-T). 3. Lineweaver-Burk plots are linear and obey Michaelis-Menten kinetics when UDP-acetylglucosamine is used as activator and UDPGA substrate concentrations are within the physiologic range present in the liver during the fed and fasted state (0.10-0.71 mM); above these concentrations, there is a discontinuity of kinetic plots as noted in other species. 4. There is no effect of fasting on the Km of BR conjugation (i.e. sum of mono- and diglucuronides) in either monkey; however, fasting is associated with lower Vm values (15-20%) in each subspecies. 5. By calculating the potential BR flux (nmol BR conjugated/min per kg) using known hepatic UDPGA concentrations, liver weights and in vitro Km and Vm, a markedly lower BR flux is observed in BoSM (58.4 nmol/min per kg) than in BrSM (91.6 nmol/min per kg). 6. Significantly higher apparent UDPGAKm and lower Vm of BR UDPG-T for conjugation of BR to BR monoglucuronide appears responsible in part for the four- to five-fold elevations in unconjugated BR in the liver and plasma in the fasted BoSM.     

Analysis of the renin-angiotensin system during fasting in adult male rabbits.

Caloric deprivation for 3 days in adult male rabbits induced significant increases in daily urinary Na+ excretion, urinary volume and fluid intake as previously reported. These changes were accompanied by: (a) a significant reduction in plasma renin concentration; (b) an unchanged plasma renin activity; (c) a marked increase in the plasma angiotensinogen concentration; (d) a significant reduction in plasma angiotensin I; and (e) a significant increase in plasma angiotensin II. In a separate group of adult male rabbits, 3 days of caloric deprivation significantly increased the amount of converting enzyme in pulmonary parenchymal tissue. These findings correlate with the previously reported enhancement of mineralocortical hormone secretion and limiting effect of the latter on the natriuresis of caloric withdrawal. Since the increased mineralocortical hormone secretion does not prevent the natriuresis, the possibility that these striking changes in the components of the renin-angiotensin system during caloric deprivation may exert intrarenal effects is discussed.